The present invention relates to a novel method for the treatment and promotion of healing of bone fractures and osteotomies in warm-blooded animals including humans, by the local application of 24,25-dihydroxycholecalciferol (24,25-dihydroxy vitamin D.sub.3, hereinafter "24,25(OH).sub.2 D.sub.3 "). The invention further relates to novel compositions comprising 24,25(OH).sub.2 D.sub.3 adapted for the local application to the sites of bone fractures or osteotomies in accordance with the method of the invention.
Vitamin D.sub.3, cholecalciferol, has been long known to be associated with bone formation. Several publications provided evidence that 24,25-dihydroxycholecalciferol (24,25(OH).sub.2 D.sub.3) is the active metabolite in this process. (Bordier, P. A. et al., J. Clin. Endocrinol. Metab. 46, 284 (1978); Kanis, J. A. et al., Br. Med. J. 1, 1382 (1978); Ornoy, A. et al., Nature 276, 517 (1978); and Endo, J. H. et al., Nature 286, 262 (1980). More recently Brumbaugh et al., Am. J. Pathology 106, 171 (1982); Dekel, S. et al., Clin. Sci. 65, 429 (1983); and Blazheevich, N. V. et al., Vopr. Med. Chim. 28 (6), 98-105 (1982) showed that systemic administration of 24,25(OH).sub.2 D.sub.3 promotes bone repair and union in experimental fractures. In all these studies, 24,25(OH).sub.2 D.sub.3 was administered to the animals or human patients by intravenous or subcutaneous injection into the muscle or by the oral route, and there was no indication nor any hint in the prior art that local administration to the fracture site of this vitamin D.sub.3 metabolite might have any effect on fracture healing.